Is DRC4 p.Asp343= (c.1029C>T) pathogenic?

DRC4 p.Asp343= (c.1029C>T) is classified Benign/Likely benign in DRC4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Rare (popmax 0.883%, afr); Associated with primary ciliary dyskinesia 33.

What condition is associated with DRC4 p.Asp343= (c.1029C>T)?

DRC4 p.Asp343= (c.1029C>T) is associated with primary ciliary dyskinesia 33 (ClinVar).

How common is DRC4 p.Asp343= (c.1029C>T) in the general population?

DRC4 p.Asp343= (c.1029C>T) is rare (popmax 0.883%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DRC4 p.Asp343=

c.1029C>T · rs7205066 · VCV707699

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.883%, afr)

Conditions

primary ciliary dyskinesia 33

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11
Overall
CADD	0.149	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.883% African / African-American · 658/74,478 alleles

Filtering AF 0.828% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.805%

Overall 0.0524% 833/1,590,618 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.883%	113
Middle Eastern	0.0692%	1,445
Remaining individualsnot grpmax-eligible	0.0503%	1,987
Admixed American	0.0423%	2,363
European (non-Finnish)	0.0095%	10,531
East Asian	0.0069%	14,483
South Asian	0.00229%	43,728

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DRC4
Protein: p.Asp343=
Coding: c.1029C>T
MANE Select: NM_001481
dbSNP: rs7205066
Type: single nucleotide variant
Location: chr16:90040317 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 343: a UniProt-annotated variant site (in cild33; loss of localization to cilia; abnormal cilia with axonemal disorganization)

Full DRC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DRC4 c.495+1G>T Likely pathogenic ★★ same condition
DRC4 p.Gln357Ter Pathogenic ★★ same condition
DRC4 p.Ala280Thr Uncertain significance ★★ ⚠ same condition
DRC4 p.Ala460Pro Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg143Trp Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg164Trp Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg203Gln Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg278Cys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/drc4-p-asp343 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown